1. Nucleotides and Nucleic Acids

2. Definitions Nucleic acids are polymers of nucleotides In eukaryotic cells nucleic acids are either: Deoxyribose nucleic acids (DNA) Ribose nucleic acids (RNA) Messenger RNA (mRNA) Transfer RNA (tRNA) Ribosomal RNA (tRNA) Nucleotides are carbon ring structures containing nitrogen linked to a 5- carbon sugar (a ribose) 5-carbon sugar is either a ribose or a deoxy-ribose making the nucleotide either a ribonucleotide or a deoxyribonucleotide

3. Nucleic Acid Function DNA Genetic material - sequence of nucleotides encodes different amino acids RNA Involved in the transcription/translation of genetic material (DNA) Genetic material of some viruses

4. Nucleotide Function Building blocks for DNA and RNA Intracellular source of energy - Adenosine triphosphate (ATP) Second messengers - Involved in intracellular signaling (e.g. cyclic adenosine monophosphate [cAMP]) Intracellular signaling switches (e.g. G-proteins)

5. Nucleotide Structure Despite the complexity and diversity of life the structure of DNA is dependent on only 4 different nucleotides Diversity is dependent on the nucleotide sequence All nucleotides are 2 ring structures composed of: 5-carbon sugar :  -D-ribose (RNA)  -D-deoxyribose (DNA) Base Purine Pyrimidine Phosphate group A nucleotide WITHOUT a phosphate group is a NUCLEOSIDE

6. Nucleotide Structure - 1 Sugars O HOCH 2 5’ 1’ 4’ 3’2’ O HOCH 2 OH O HOCH 2 OH H Ribose Deoxyribose Generic Ribose Structure N.B. Carbons are given numberings as a prime

7. Nucleotide Structure - 2 Bases - Purines N N N N 1 2 3 4 5 6 7 8 9 Adenine Guanine A G N N N N H NH 2 N N N N H O H

8. Nucleotide Structure - 3 Bases - Pyrimidines N N 5 6 1 2 3 4 Thymine Cytosine NH N O T O H H3CH3C C N N NH 2 O H

9. Nucleotide Structure - 4 Bases - Pyrimidines N N 5 6 1 2 3 4 Uracil NH N O U O H Thymine is found ONLY in DNA. In RNA, thymine is replaced by uracil Uracil and Thymine are structurally similar

10. Nucleotide Structure - 4 Phosphate Groups Phosphate groups are what makes a nucleoside a nucleotide Phosphate groups are essential for nucleotide polymerization P O O O OX Basic structure:

11. Nucleotide Structure - 4 Phosphate Groups Number of phosphate groups determines nomenclature P O O O OCH 2 P O O O P O O O O Monophosphate e.g. AMP Diphosphate e.g. ADP Free = inorganic phosphate (Pi) Free = Pyro- phosphate (PPi)

12. Triphosphate e.g. ATP P O O O P O O O OP O O O CH 2 Nucleotide Structure - 4 Phosphate Groups No Free form exists

13. Nucleotide Structure - 4 Base-Sugar-PO 4 2- P O O O O N N 5 6 1 2 3 4 O C 5’ 1’ 4’ 3’2’ OH Monophosphate

14. P P (PPi) Nucleic Acid Structure Polymerization PPP S N C PPP S N C + PPP S N C P S N C Phosphodiesterase

15. Nucleic Acid Structure Polymerization Nucleotide Sugar Phosphate “backbone”

16. Nucleic Acid Structure Polymerization T A AG CC 5’ 3’ TAGCAC 5’ 3’ Bases Sugar Phosphate “backbone”

17. Nucleic Acid Structure “Base Pairing” RNA [normally] exists as a single stranded polymer DNA exists as a double stranded polymer DNA double strand is created by hydrogen bonds between nucleotides Nucleotides always bind to complementary nucleotides AT CG (2 H-bonds) (3 H-bonds)

18. Nucleic Acid Structure “Base Pairing”

19. Nucleic Acid Structure “Base Pairing” RNA is [usually] single stranded Base pairing can occur in RNA but is usually within the same strand

20. Nucleic Acid Structure “Base Pairing” T A AG CC 3’ T C GG TA 5’ DNA base-pairing is antiparallel i.e. 5’ - 3’ (l-r) on top : 5’ - 3’ (r-l) on

21. Nucleic Acid Structure Antiparallel Base Pairing Why antiparallel DNA base-pairing? - Need to shield the genetic information - Is the only conformational structure to allow double helix formation

22. Nucleic Acid Structure The double helix First determined by Watson & Crick in 1953 Shape and size is uniform for all life (i.e. DNA is identical) Most energy favorable conformation for double stranded DNA to form Without anti-parallel base pairing this conformation could not exist Structure consists of “major” grooves and “minor” grooves Major grooves are critical for binding proteins that regulate DNA function

23. Nucleic Acid Structure The double helix Major Groove Minor Groove